BACKGROUND AND PURPOSE: 

• Noonan syndrome is an autosomal dominant disorder that occurs in approximately 1 in 1,000 to 2,500 people 
• It is the most common single gene disorder seen with NT and a well-known finding in association with cystic hygroma   
• Ali et al. (Prenatal Diagnosis, 2017) sought to determine the prevalence of Noonan syndrome in fetuses with increased nuchal translucency (NT) thickness in the first trimester of pregnancy 

METHODS: 

• Retrospective cohort study 
• Centers all with AIUM certified prenatal diagnostic units, and NTQR certified teams  
• Inclusion criteria 
  • First trimester NT measurement ≥ 3 mm 
  • Normal karyotype by either a CVS or an amniocentesis  
  • Prenatal molecular genetic testing for Noonan syndrome available 
• 2 labs reported results 
  • Lab 1: 9 Noonan syndrome genes plus Costello and CFC syndromes  
  • Lab 2: 7 Noonan syndrome genes plus Costello and CFC syndromes  
    • Two genes not screened were NRAS and RIT1, but only make up 5% of Noonan syndrome postnatally  
  • Costello and CFC (cardiofaciocutaneous) syndromes have overlapping features with Noonan syndrome
• Positive report: Known pathogenic variants in any tested gene 
• Negative report: Variants of uncertain clinical significance or no variants 

RESULTS: 

• 804 fetuses had NT measurement of ≥ 3 mm 
  • Median NT was 3.6 mm 
• 302 (37.6%) had karyotyping by CVS or amnio 
  • 200 (66.2%) had normal results 
• No molecular testing in 161 fetuses with normal karyotype (mean NT thickness 4.3 mm)  
• 39 fetuses with normal karyotype (median NT thickness of 4.0 mm) were screened for Noonan syndrome  
• 4 fetuses (10.3%) had variants consistent with this Noonan syndrome 

CONCLUSION: 

• Increased nuchal translucency (NT) is associated with a 10% risk of Noonan syndrome 
• Confirms previously reported literature (see Croonen et al; European Journal of Human Genetics, 2013) 

Learn More – Primary Sources:  

Ali et al. Testing for Noonan syndrome after increased nuchal translucency 

Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings 

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